The present invention relates to acid addition salts of lenalidomide, pharmaceutical compositions containing the salts, and methods of purifying lenalidomide base using the salts.
Lenalidomide=3-(4-amino-1-oxo-3H-isoindol-2-yl)piperidine-2,6-dione is a pharmaceutically active compound useful for the treatment of some blood diseases such as multiple myeloma or myelodysplasic syndrome and is represented by the formula (I).

The compound of formula (I), unless stated otherwise, is a racemic compound.
The marketed pharmaceutical composition is an immediate release capsule sold under the brand name REVLIMID® (by Celgene), that contains lenalidomide as a hemihydrate of the free base. Lenalidomide was first described in U.S. Pat. No. 5,635,517 and was generically described as including salts thereof, but no actual salt of lenalidomide was shown.
Lenalidomide is a poorly water soluble compound with the highest solubility in 0.1N HCl (18 mg/ml) and lower solubility at pH 4.6, 6.8 and 7.4 (0.4-0.5 mg/ml).
While the commercially useful lenalidomide free base form is a hemihydrate, a patent application WO 2005/023192 describes 8 forms of lenalidomide base: three unsolvated forms, the hemihydrate, a dihydrate, an acetone hemisolvate, an acetonitrile solvate, and a dehydrated form of the dihydrate. However, nothing is known whether and under which conditions lenalidomide may form isolatable acid addition salts and an improvement in this respect is desirable.
Processes for making lenalidomide were disclosed in U.S. Pat. No. 5,635,517, WO2006/028964 and WO2005/005409. In general, these processes involve a cyclization and reduction steps. These processes are apparently accompanied by the formation of impurities but no purification process has been disclosed. It would be therefore desirable to have purification techniques for preparing lenalidomide of a high purity, particularly lenalidomide of a pharmaceutical grade.